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Dystrophin deficiency reduces atherosclerotic plaque development in ApoE- mice.

Shami A, Knutsson A, Dunér P, Rauch U, Bengtsson E, Tengryd C, Murugesan V, Durbeej M, Gonçalves I, Nilsson J, Hultgårdh-Nilsson A - Sci Rep (2015)

Bottom Line: Dystrophin of the dystrophin-glycoprotein complex connects the actin cytoskeleton to basement membranes and loss of dystrophin results in Duchenne muscular dystrophy.ApoE- mdx mice were also found to have a reduced fraction of CD3(+) T cells in the spleen and lower levels of cytokines and monocytes in the circulation.The present study is the first to demonstrate a role for dystrophin in atherosclerosis and unexpectedly shows that this primarily involves immune cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.

ABSTRACT
Dystrophin of the dystrophin-glycoprotein complex connects the actin cytoskeleton to basement membranes and loss of dystrophin results in Duchenne muscular dystrophy. We have previously shown injury-induced neointima formation of the carotid artery in mice with the mdx mutation (causing dystrophin deficiency) to be increased. To investigate the role of dystrophin in intimal recruitment of smooth muscle cells (SMCs) that maintains plaque stability in atherosclerosis we applied a shear stress-modifying cast around the carotid artery of apolipoprotein E (ApoE)- mice with and without the mdx mutation. The cast induces formation of atherosclerotic plaques of inflammatory and SMC-rich/fibrous phenotypes in regions of low and oscillatory shear stress, respectively. Unexpectedly, presence of the mdx mutation markedly reduced the development of the inflammatory low shear stress plaques. Further characterization of the low shear stress plaques in ApoE- mdx mice demonstrated reduced infiltration of CD3(+) T cells, less laminin and a higher SMC content. ApoE- mdx mice were also found to have a reduced fraction of CD3(+) T cells in the spleen and lower levels of cytokines and monocytes in the circulation. The present study is the first to demonstrate a role for dystrophin in atherosclerosis and unexpectedly shows that this primarily involves immune cells.

No MeSH data available.


Related in: MedlinePlus

Reduced atherosclerotic burden in ApoE/mdx mice.Representative sections of Masson’s trichrome stain from low shear stress (a–b) and oscillatory shear stress (c–d) plaques in ApoE- and ApoE/mdx mice. Plaque size represented by plaque/media ratio (e) and total plaque size (f). Quantification of Oil Red O-stained flat preparations of aortas from ApoE and ApoE/mdx mice (g). Scale bars represent 100 μm and Mann-Whitney U test was used.
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f1: Reduced atherosclerotic burden in ApoE/mdx mice.Representative sections of Masson’s trichrome stain from low shear stress (a–b) and oscillatory shear stress (c–d) plaques in ApoE- and ApoE/mdx mice. Plaque size represented by plaque/media ratio (e) and total plaque size (f). Quantification of Oil Red O-stained flat preparations of aortas from ApoE and ApoE/mdx mice (g). Scale bars represent 100 μm and Mann-Whitney U test was used.

Mentions: In the ApoE/mdx mouse, carotid artery plaques developing in the low shear stress region were smaller than the plaques formed in the same region in ApoE mice (P < 0.0001, Fig. 1a–f). Plaque sizes in the oscillatory shear stress region were similar in ApoE and ApoE/mdx mice. Development of atherosclerosis in the aorta, as assessed by en face Oil Red O staining, was reduced by almost 60% in ApoE/mdx mice as compared to ApoE mice (Fig. 1g and Supplementary Fig. S3).


Dystrophin deficiency reduces atherosclerotic plaque development in ApoE- mice.

Shami A, Knutsson A, Dunér P, Rauch U, Bengtsson E, Tengryd C, Murugesan V, Durbeej M, Gonçalves I, Nilsson J, Hultgårdh-Nilsson A - Sci Rep (2015)

Reduced atherosclerotic burden in ApoE/mdx mice.Representative sections of Masson’s trichrome stain from low shear stress (a–b) and oscillatory shear stress (c–d) plaques in ApoE- and ApoE/mdx mice. Plaque size represented by plaque/media ratio (e) and total plaque size (f). Quantification of Oil Red O-stained flat preparations of aortas from ApoE and ApoE/mdx mice (g). Scale bars represent 100 μm and Mann-Whitney U test was used.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561962&req=5

f1: Reduced atherosclerotic burden in ApoE/mdx mice.Representative sections of Masson’s trichrome stain from low shear stress (a–b) and oscillatory shear stress (c–d) plaques in ApoE- and ApoE/mdx mice. Plaque size represented by plaque/media ratio (e) and total plaque size (f). Quantification of Oil Red O-stained flat preparations of aortas from ApoE and ApoE/mdx mice (g). Scale bars represent 100 μm and Mann-Whitney U test was used.
Mentions: In the ApoE/mdx mouse, carotid artery plaques developing in the low shear stress region were smaller than the plaques formed in the same region in ApoE mice (P < 0.0001, Fig. 1a–f). Plaque sizes in the oscillatory shear stress region were similar in ApoE and ApoE/mdx mice. Development of atherosclerosis in the aorta, as assessed by en face Oil Red O staining, was reduced by almost 60% in ApoE/mdx mice as compared to ApoE mice (Fig. 1g and Supplementary Fig. S3).

Bottom Line: Dystrophin of the dystrophin-glycoprotein complex connects the actin cytoskeleton to basement membranes and loss of dystrophin results in Duchenne muscular dystrophy.ApoE- mdx mice were also found to have a reduced fraction of CD3(+) T cells in the spleen and lower levels of cytokines and monocytes in the circulation.The present study is the first to demonstrate a role for dystrophin in atherosclerosis and unexpectedly shows that this primarily involves immune cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.

ABSTRACT
Dystrophin of the dystrophin-glycoprotein complex connects the actin cytoskeleton to basement membranes and loss of dystrophin results in Duchenne muscular dystrophy. We have previously shown injury-induced neointima formation of the carotid artery in mice with the mdx mutation (causing dystrophin deficiency) to be increased. To investigate the role of dystrophin in intimal recruitment of smooth muscle cells (SMCs) that maintains plaque stability in atherosclerosis we applied a shear stress-modifying cast around the carotid artery of apolipoprotein E (ApoE)- mice with and without the mdx mutation. The cast induces formation of atherosclerotic plaques of inflammatory and SMC-rich/fibrous phenotypes in regions of low and oscillatory shear stress, respectively. Unexpectedly, presence of the mdx mutation markedly reduced the development of the inflammatory low shear stress plaques. Further characterization of the low shear stress plaques in ApoE- mdx mice demonstrated reduced infiltration of CD3(+) T cells, less laminin and a higher SMC content. ApoE- mdx mice were also found to have a reduced fraction of CD3(+) T cells in the spleen and lower levels of cytokines and monocytes in the circulation. The present study is the first to demonstrate a role for dystrophin in atherosclerosis and unexpectedly shows that this primarily involves immune cells.

No MeSH data available.


Related in: MedlinePlus